Genetic Predisposition and Renal Allograft Failure

Khan, Faisal Ali Anwarali; Agrawal, Swati; Agrawal, Suraksha

doi:10.1007/bf03256459

Cited by 6 publications

(5 citation statements)

References 113 publications

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“…In addition to human leukocyte antigen loci, several genes encoding cytokines and their receptors have been recently suggested to play an important role in the process of rejection (1)(2)(3).…”

mentioning

confidence: 99%

Genetic Variability of Major Inflammatory Mediators Has No Impact on the Outcome of Kidney Transplantation

Brabcova

Petrášek²,

Hřibová³

et al. 2007

Transplantation

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mentioning

confidence: 99%

Genetic Variability of Major Inflammatory Mediators Has No Impact on the Outcome of Kidney Transplantation

Brabcova

Petrášek²,

Hřibová³

et al. 2007

Transplantation

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“…Various researchers have sought to identify markers related to the occurrence of AR such as cytochrome enzyme (CYP3A), multidrug resistance (MDR1) gene and cytokine gene polymorphisms of renal transplant allografts (Khan & Agrawal, 2006;Golling et al, 2009).…”

confidence: 99%

“…Cytokines and their receptors, growth factors and proteins as substrates of immunosuppressive drugs all have an impact on graft success (Khan & Agrawal, 2006). Cytokine polymorphisms have been related to reduced metabolism, efflux and effect of CNIs (Loucaidou et al, 2005).…”

confidence: 99%

Genetic association of interleukin‐2, interleukin‐4, interleukin‐6, transforming growth factor‐β, tumour necrosis factor‐α and blood concentrations of calcineurin inhibitors in Turkish renal transplant patients

Seyhun

Çiftçi

Kekik

et al. 2015

Int J Immunogenetics

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Cytokines are essential for the control of the immune response as most of the immunosuppressive drugs target cytokine production or their action. The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are immunosuppressive drugs widely used after renal transplantation to prevent allograft rejection. They are characterized by large interindividual variability in their pharmacokinetics; therefore, monitoring their blood concentrations is important to predict their optimal dosage following transplantation. Calcineurin inhibitors inhibit the phosphatase activity of calcineurin, thereby suppressing the production of other cytokines such as transforming growth factor (TGF-β), tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-2, and IL-4. The aim of this study was to investigate the relationship between polymorphisms of cytokines and blood concentrations of CNIs in renal transplant patients. The study included 53 CsA-treated renal transplant patients and 37 tacrolimus-treated renal transplant patients. Cytokine polymorphisms were analysed using polymerase chain reaction (PCR) sequence-specific primers with the cytokine CTS-PCR-sequence-specific primers Tray Kit; University of Heidelberg. Blood concentrations of CNIs were determined with Cloned Enzyme Donor Immunoassay (CEDIA) method. Patients with TC genotype of TGF-β at codon 10 had lower CsA blood concentrations than the TT and CC genotypes (P = 0.005) at 1 month in CsA treatment group. The ratio of blood concentration/dose of CsA for patients with TGF-β1-codon 10 TC genotype was lower than for patients with TT, CC genotypes, and the dose given to these patients was higher in the first month (P = 0.046). The ratio of blood concentration/dose of CsA for patients with IL-2-330 GG genotype was higher than for patients with GT, TT genotypes, and the dose given to these patients was lower at first month and sixth months (P = 0.043, P = 0.035 respectively). The tacrolimus blood concentrations were significantly higher in patients with the genotype GG of IL-2-330 (P = 0.012) at the third month. Patients who had the TC genotype TGF-β codon 10 had lower CsA blood concentrations and this group had higher acute rejection (P = 0.033). These results suggest that the genotyping for TGF-β-codon 10, IL-2-330 and IL-6-174 polymorphisms may help individualized immunosuppressive dosage regiments.

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“…60 Polymorphisms in genes encoding for interferon gamma or tumor necrosis factor alpha are also being evaluated to taper immunosuppression regimens to each KTRs' needs. [61][62][63][64][65] Pharmacogenomics also offer a more proactive approach to immunosuppression choices. Pharmacogenomics encompass the genetic determinants of pharmacokinetics and pharmacodynamics.…”

Section: Future Directions In Personalized Therapymentioning

confidence: 99%

Changing Paradigms in the Management of Rejection in Kidney Transplantation

Maier

Takano

Sapir‐Pichhadze

2017

Can J Kidney Health Dis

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Purpose of review:P4 medicine denotes an evolving field of medicine encompassing predictive, preventive, personalized, and participatory medicine. Using the example of kidney allograft rejection because of donor-recipient incompatibility in human leukocyte antigens, this review outlines P4 medicine’s relevance to the various stages of the kidney transplant cycle.Sources of information:A search for English articles was conducted in Medline via OvidSP (up to August 18, 2016) using a combination of subject headings (MeSH) and free text in titles, abstracts, and author keywords for the concepts kidney transplantation and P4 medicine. The electronic database search was expanded further on particular subject headings.Findings:Available histocompatibility methods exemplify current applications of the predictive and preventive domains of P4 medicine in kidney transplant recipients’ care. Pharmacogenomics are discussed as means to facilitate personalized immunosuppression regimens and promotion of active patient participation as a means to improve adherence.Limitations:For simplicity, this review focuses on rejection. P4 medicine, however, should more broadly address health concerns in kidney transplant recipients, including competing outcomes such as infections, malignancies, and cardiovascular disease. This review highlights how biomarkers to evaluate these competing outcomes warrant validation and standardization prior to their incorporation into clinical practice.Implications:Consideration of all 4 domains of the P4 medicine framework when caring for and/or studying kidney transplant recipients has the potential of increasing therapeutic efficiency, minimizing adverse effects, decreasing health care costs, and maximizing wellness. Technologies to gauge immune competency, immunosuppression requirements, and early/reversible immune-mediated injuries are required to optimize kidney transplant care.

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Genetic Predisposition and Renal Allograft Failure

Cited by 6 publications

References 113 publications

Genetic Variability of Major Inflammatory Mediators Has No Impact on the Outcome of Kidney Transplantation

Genetic Variability of Major Inflammatory Mediators Has No Impact on the Outcome of Kidney Transplantation

Genetic association of interleukin‐2, interleukin‐4, interleukin‐6, transforming growth factor‐β, tumour necrosis factor‐α and blood concentrations of calcineurin inhibitors in Turkish renal transplant patients

Changing Paradigms in the Management of Rejection in Kidney Transplantation

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